US 2010-0279970A1, herein incorporated by reference in its entirety, discloses a clinically significant reduction of intraocular pressure using an Adenosine A1 receptor agonist in human subjects having glaucoma.
US 2011-0123622A1, which is also incorporated by reference in its entirety as if individually set forth, describes formulations of Compound A comprising:
Ingredient% w/vCompound A, micronized0.152-2.42Sodium CMC, low viscosity0.7Benzalkonium Chloride 0.01Polysorbate 800.3Citric Acid Monohydrate0.15-0.3Glycine   0-0.10NaClTBD (q.s.270-300 mOsm)NaOH/HCl (pH adjustmentpH 5.1 ± 0.1Purified Waterq.s. 100.00
However, over time, there can be some variability in the chemical stability of these formulations at for example 25° Celsius, and, particle size growth can occur under some conditions in some of the formulations described in US 2011-0123622A1. Additionally, after prolonged storage of months to years, the suspended drug particles can settle to the bottom of the formulation making their re-suspension with shaking to re-form a homogeneous suspension difficult.
Accordingly, there exists a need to develop new ophthalmic formulations with (i) enhanced chemical stability, (ii) limited particle size growth over extended storage periods, and (iii) more rapid and efficient re-suspension of the active pharmaceutical ingredient (API) particles after storage. In addition, there exists a need to develop further ophthalmic formulations for delivering Compound A and a process for manufacturing the ophthalmic formulation.